Recent Progress in tRNA Structural Analysis

Abstract

tRNA plays a central role in the expression of genetic information. Structural studies on tRNA have a dual goal. One is to learn about the three-dimensional structure of this molecule in sufficient detail so we can understand its solution chemistry, reactivity, and stability. And the other is to identify those structural features that are used by nature in the translation mechanism. How is tRNA recognized by enzymes and components of the ribosomal machinery so that it can carry out its functions? Structural studies eventually lead to functional considerations.

We now understand a great deal about the three-dimensional structure of one tRNA molecule, yeast tRNA^phe. The first tRNA was sequenced by Holley and coworkers (1965); at the present time there are almost 100 sequences known (Gauss and Sprinzl 1978). These sequences have amply verified the universality of the cloverleaf folding of the molecule. By 1973, the three-dimensional folding of yeast tRNA^phe was solved by X-ray diffraction analysis of orthorhombic crystals (Kim et al. 1973). In 1974 higher resolution analyses of both the orthorhombic and monoclinic yeast tRNA^phe crystals revealed finer details of tertiary base-base interactions (Kim et al. 1974a; Robertus et al. 1974). Subsequent analysis and refinement of the molecule have produced a startlingly clear picture of the three-dimensional conformation of this one tRNA molecule. We can see how the invariant nucleotides are utilized in the three-dimensional folding of yeast tRNA^phe and from this we can predict how this tRNA molecule may be used as a pattern for understanding the three...